Colorectal cancer is the third most common cancer diagnosed in the United States, and affects approximately 150,000 patients each year. Even though fatality rates among men and women have been decreasing over time, colorectal cancer remains the third leading cause of cancer-related death.
Recently published results of a phase II clinical trial led by Andrea Cercek, MD, at Memorial Sloan Kettering Cancer Center, identified 14 patients with mismatch repair–deficient colorectal cancer who went into remission after treatment with the programmed death 1 (PD-1) inhibitor, dostarlimab. This was published in The New England Journal of Medicine, on June 23rd, 2022.
Whereas standard treatment for locally advanced rectal cancer involves neoadjuvant chemoradiotherapy followed by surgical resection, individuals harboring a deficiency in mismatch repair often require a PD-1 checkpoint blockade to improve treatment outcomes.
According to The National Cancer Institute, PD-1 is a protein found on T cells that helps regulate the immune system. However, when it binds to another protein called PD-L1, it stops T cells from killing other cells, including cancer cells. Due to this, agents called PD-1 inhibitors are often used in patients with elevated PD-1 expression to stop this cascade.
Taken together, the findings of this study suggest that patients with this particular disease may benefit from a different form of treatment than usual, as standard of care therapies are not always effective.
“Surgery and radiation have permanent effects on fertility, sexual health, bowel, and bladder function,” stated Dr. Cercek in an institutional press release. “The implications for quality of life are substantial, especially in those where standard treatment would impact childbearing potential. As the incidence of rectal cancer is rising in young adults, this approach can have a major impact.”
This study enrolled 14 patients with mismatch repair–deficient stage II or III rectal adenocarcinoma who received no prior immunotherapy, chemotherapy, or radiation for their primary tumor. Participants were administered single-agent dostarlimab every 3 weeks for 6 months. Those who demonstrated a complete clinical response after completing the immunotherapy regimen would not require additional chemoradiotherapy and surgery.
To date, every patient who completed dostarlimab treatment and underwent at least 6 months of follow-up demonstrated a complete clinical response. The researchers state that there was no evidence of tumors on PET or MRI scans, biopsy, digital rectal examination, or endoscopic evaluation. Moreover, not a single patient required chemoradiotherapy or surgery after study treatment, as there were no instances of recurrence or progression during follow-up.
Although adverse events were reported in all patients, they were not severe. The most common adverse events included mild (grade 1 or 2) fatigue, nausea, rash, and pruritus; one patient experienced thyroid-function abnormalities.
A longer follow-up is required to determine response duration, but the investigators can conclude that locally advanced, mismatch repair–deficient rectal cancer is incredibly responsive to PD-1 blockade, in just 6 months.
“It’s incredibly rewarding,” Cercek told CBS News, “to get these happy tears and happy emails from the patients in this study who finish treatment and realize, ‘Oh my God, I get to keep all my normal body functions that I feared I might lose to radiation or surgery.'”
________________________________________________________________________________________________________________
References
American Cancer Society. (2022, January 12). Colorectal cancer statistics: How common is colorectal cancer? Key Statistics for Colorectal Cancer. Retrieved August 2, 2022, from https://www.cancer.org/cancer/colon-rectal-cancer/about/key-statistics.html
Cercek, A., Lumish, M., Sinopoli, J., Weiss, J., Shia, J., Lamendola-Essel, M., El Dika, I. H., Segal, N., Shcherba, M., Sugarman, R., Stadler, Z., Yaeger, R., Smith, J. J., Rousseau, B., Argiles, G., Patel, M., Desai, A., Saltz, L. B., Widmar, M., … Diaz, L. A. (2022). PD-1 blockade in mismatch repair–deficient, locally advanced rectal cancer. New England Journal of Medicine, 386(25), 2363–2376. https://doi.org/10.1056/nejmoa2201445
Larnaud, N. (2022, June 8). Every patient in this experimental drug trial saw their cancer disappear, researchers say. CBS News. Retrieved July 28, 2022, from https://www.cbsnews.com/news/rectal-cancer-drug-trial-immunotherapy-dostarlimab-study/
National Institutes of Health. (n.d.). NCI Dictionary of Cancer terms. National Cancer Institute. Retrieved August 2, 2022, from https://www.cancer.gov/publications/dictionaries/cancer-terms/def/pd-1
Sunday, J. 5. (2022, June 5). Asco 2022: 100% complete response rate in MMRD locally advanced rectal cancer seen in pivotal ‘immunoablative’ neoadjuvant immunotherapy clinical trial. Memorial Sloan Kettering Cancer Center. Retrieved July 28, 2022, from https://www.mskcc.org/news-releases/asco-2022-100-complete-response-rate-mmrd-locally-advanced-rectal-cancer-seen-pivotal-immunoablative-neoadjuvant-immunotherapy-clinical-trial